This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sacks, F. M. Search for Related Content PubMed PubMed Citation Articles by Sacks, F. M.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1689.)
© 2006 American Heart Association, Inc.

Editorials

Soy Protein, Isoflavones, and Cardiovascular Health

A Summary of a Statement for Professionals From the American Heart Association Nutrition Committee

Frank M. Sacks; Alice Lichtenstein; Linda Van Horn; William Harris; Penny Kris-Etherton; Mary Winston for the AHA Nutrition Committee

From the Cardiovascular Division and Channing Laboratory (F.M.S.), the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; the Cardiovascular Nutrition Laboratory (A.L.), Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Mass; the Department of Preventive Medicine, Feinberg School of Medicine (L.V.H.), Northwestern University, Chicago, Ill; Mid America Heart Institute of St. Luke’s Health System (W.H.), Kansas City, Mo; and the Departments of Nutritional Sciences and Integrative Biosciences (P.K.-E.), the Pennsylvania State University, University Park, Pa. M.W. is an AHA consultant.

Correspondence to Frank M. Sacks, MD, Department of Nutrition, Harvard School of Public Health, Boston, MA 02115. E-mail fsacks{at}hsph.harvard.edu

	Introduction

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
This editorial summarizes the recent American Heart Association (AHA) Science Advisory on soy protein and isoflavones (phytoestrogens) published in the February 21, 2006, issue of Circulation.¹ Soy protein and isoflavones have gained considerable attention for their potential role in improving risk factors for cardiovascular disease. This scientific advisory report assesses the more recent work published on soy protein and its component isoflavones. In 22 randomized trials, isolated soy protein with isoflavones compared with milk or other proteins decreased LDL cholesterol concentrations in most studies; the average effect was approximately 3%. This reduction is very small compared with the large amount of soy protein tested in these studies, averaging 50 g, approximately half the usual total daily protein intake. No significant effects were evident on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure. Among 19 studies of soy isoflavones, the average effect on LDL cholesterol and other lipid risk factors was nil. Soy protein or isoflavones have not been shown to lessen vasomotor symptoms of menopause, and results are mixed regarding slowing of postmenopausal bone loss. The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established; evidence from clinical trials is meager and cautionary as regards a possible adverse effect. For this reason, use of isoflavone supplements in food or pills is not recommended. Thus, earlier research indicating that soy protein compared with other proteins has clinically important favorable effects has not enjoyed confirmation. In contrast, many soy products should be beneficial to cardiovascular and overall health because of their high content of polyunsaturated fats, fiber, vitamins, and minerals and low content of saturated fat.

In October 1999, the US Food and Drug Administration (FDA) approved labeling for foods containing soy protein as protective against coronary heart disease.² The FDA based this decision on clinical studies showing that at least 25 g soy protein per day lowered total and LDL cholesterol. The FDA requires for the claim that a serving contain at least 6.25 g soy protein, 25% of the necessary daily amount, 25 g, expecting that foods containing soy protein would be eaten at least 4 times per day. The FDA also stated, "the evidence did not support a significant role for soy isoflavones in cholesterol-lowering effects of soy protein."

In 2000, the AHA Nutrition Committee released a scientific advisory on soy protein and CVD.³ Since then, many well-controlled studies on soy protein and soy-derived isoflavones substantially added to the knowledge base. This scientific advisory report assesses the more recent work published on soy protein and its component isoflavones, focusing on blood LDL cholesterol and other cardiovascular disease risk factors, HDL cholesterol, triglycerides, lipoprotein(a), and blood pressure. The medical literature was searched comprehensively for original research publications on the effects of soy protein or isoflavones on cardiovascular disease risk factors, and all controlled trials that separately listed soy protein and isoflavone content were used. Most studies exchanged soy protein for other dietary proteins, and this evidence is evaluated in this report. Much less is known about the potential impact on risk factors for CVD of increasing total protein intake by adding soy or other plant protein in place of carbohydrate or fat; this important dietary change is currently being studied.

Animal proteins raise blood cholesterol concentrations in several animal species fed cholesterol-free semi-synthetic diets.^4,5 Casein, the most prevalent protein in milk, has been the most often used, although other animal proteins such as pork and beef protein do the same. In contrast, when soy protein is substituted for the animal protein, hypercholesterolemia does not occur. Diets similar to those eaten by humans, based on either soy protein or casein, were fed to rabbits, and casein produced hypercholesterolemia as expected.⁶ However, when the same diets were fed to healthy people, the protein source did not affect blood cholesterol.^6,7 In the late 1970s and early 1980s, Sirtori and colleagues found that diets high in soy protein, replacing nearly all the animal protein, substantially reduced blood cholesterol by 20% to 30% in severe hypercholesterolemia.⁸ Because the soy protein diets were also reduced in saturated fat and cholesterol and increased in polyunsaturated fat, and because the patients also often lost weight on the dietary protocols, the results were often confounded.

A meta-analysis published in 1995 found a trend that soy protein selectively reduced blood cholesterol in direct proportion to the degree of hypercholesterolemia.⁹ For example, in those with severely elevated blood cholesterol (>335 mg/dL), soy protein reduced blood cholesterol by 20%, but if the initial blood cholesterol was <255 mg/dL, there was no significant effect. This meta-analysis was limited by the quality of the studies; studies were less well-controlled in people with hypercholesterolemia than in those with average cholesterol levels.

	Effects of Soy Protein with Isoflavones

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
The 3 major isoflavones found in soybeans are genistin, daidzin, and glycitin. Their abundance in soy protein preparations varies widely and depends on the processing techniques used during production.^10,11 These compounds have both estrogenic and antiestrogenic activity^12,13 and effects that are unrelated to estrogen activity.¹⁴ Because the possibility was recognized that isoflavones could be the bioactive component attributed to soy protein, studies published in the late 1990s and beyond generally stated the amount and type of isoflavones in the soy protein. In 22 randomized trials, isolated soy protein with isoflavones was compared with casein or milk protein,^15–32 wheat protein,³³ or mixed animal proteins.^34–36 The range of soy protein was 25 to 135 g per day, and of isoflavones 40 to 318 mg. LDL or non-HDL cholesterol concentrations decreased in most studies, statistically significantly in 6, with an overall effect of 3% (weighted average). A recent meta-analysis that included 10 studies published from 1995 to 2002 found a similar percentage reduction in LDL cholesterol with no dose effect.³⁷ Over all studies listed in Table 1 in the Advisory statement by Sacks et al¹, there is no apparent dose effect; the 8 studies with soy protein 50 g or more showed a similar drop in LDL cholesterol concentration to those using a smaller amount of soy, 3% overall. This cut point for daily soy protein intake, 50 g, defines a large amount, half or more of the daily average total protein intake in the US. No significant effects were evident on HDL cholesterol or triglycerides in most of the studies; the weighted average effects were very small, +1.5% for HDL cholesterol and –5% for triglycerides.

	Soy Protein Without Isoflavones

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
Soy protein, from which isoflavones were removed, was studied in 7 trials, and compared with casein or milk protein,^{15,19,25,29,38} or various animal proteins^35,36 (see Table 2 in Sacks et al¹). Two of the studies showed small significant decreases in LDL cholesterol.^35,36 These studies were very carefully controlled feeding studies, all meals being formulated according to strict nutritional specifications, and complete meals were provided to the participants. They were specifically designed to sort out the effects of the protein from the isoflavones, and showed an effect of protein but not isoflavones on LDL cholesterol. The declines in LDL cholesterol were small, 2% to 7%, relative to the large amounts of soy protein eaten daily, 50 to 55 g. However, other well-controlled studies did not find significant effects of soy protein on LDL cholesterol,^{15,19,25,29,38} and the average change across all 7 studies is only a 1% to 2% decrease. Changes generally were small in HDL cholesterol and triglycerides, and nonsignificant in 6 of the 7 trials. No dose effect is evident.

	Isoflavone Effects

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
Some studies compared soy protein that did or did not contain isoflavones,^{15,16,19,25,29,35,36,38,39–43} whereas other studies tested isoflavones in pill form compared with placebo^44–49 (see Table 3 in Sacks et al¹). A wide range of isoflavone amounts were studied. One study compared the effect of isoflavones provided with either soy or animal proteins.³⁵ Among these 19 studies, only 3 showed significant reduction in LDL cholesterol concentration,^38,41,42 and the effect among all studies (weighted average) was nil, 0%. Changes in HDL cholesterol and triglycerides were not significant and showed no trend toward an effect of isoflavones. Despite large increases in blood isoflavone concentrations, there is no indication of a dose effect on blood lipids. A recent meta-analysis concluded that isoflavones do not affect blood lipid concentrations.³⁷

	Influence of Initial Blood LDL-Cholesterol Level

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
Lichtenstein et al³⁵ and Crouse et al¹⁵ found slightly more LDL cholesterol reduction in people with LDL cholesterol above 160 to 164 mg/dL than with lower levels, although Dent et al¹⁹ did not find an effect in women with hypercholesterolemia compared with average cholesterol. However, a larger percentage reduction in LDL cholesterol in hypercholesterolemia is not evident among the 22 recent trials (Table 1, Sacks et al¹). Among studies of isoflavones, there is no relation evident between initial cholesterol and cholesterol-lowering (Table 3, Sacks et al¹).

	Influence of Serum Cholesterol-Lowering Diet

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
In 11 of the studies listed in Tables 1 to 3 of Sacks et al,¹ soy protein or isoflavones were tested in combination with a serum cholesterol-lowering diet.^{15–17,20,28,31,33,34,36,44,46} The average reduction in LDL in these studies was 2%, similar to the full group. Thus, the effect on LDL of soy protein or isoflavones does not appear to be modulated by the saturated fat and cholesterol content of the diet.

	Effects on Lipoprotein(a)

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
Lipoprotein(a), an LDL-like lipoprotein that is an independent predictor of CVD was increased by soy protein in 2 studies^21,50 and unchanged in 9 others.^{15,17,18,22,26,30–32,36} Meinertz et al²⁵ found that alcohol-extracted soy protein, lacking isoflavones, did not raise Lp(a) as found in their earlier study of intact soy protein,⁵⁰ suggesting an adverse effect of isoflavones. However, isoflavones had no effect on Lp(a) in 6 other studies,^{15,36,41,46,47,49} nor did soy protein that contained isoflavones.^{15,17,18,22,26,30–32,36}

	Effects on Blood Pressure

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
Several studies tested the effect of soy protein with isoflavones compared with casein or milk protein on blood pressure.^{18,21,26,28,33,36} Blood pressure decreased significantly in 1 study,²¹ but not in the other 5.^{18,26,28,33,36} The weighted average change is –1 mm Hg systolic blood pressure. Several studies that evaluated the effect of soy isoflavones also did not find a significant effect on blood pressure.^{36,44,46,48,51}

	Effects on Health Conditions Related to Estrogens

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
The reader is referred to the Science Advisory¹ for a summary of evidence on menopausal vasomotor symptoms, osteoporosis, and cancer of the breast, uterus, and prostate.

	Conclusions

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 
Earlier research indicating that soy protein compared with other proteins has clinically important favorable effects on LDL cholesterol and other cardiovascular disease risk factors has not enjoyed confirmation from many studies reported during the past 10 years. A very large amount of soy protein, comprising more than half of daily protein intake, may lower LDL cholesterol by just a few percent when it replaces dairy protein or a mixture of animal proteins. The evidence favors soy protein rather than soy isoflavones as the responsible nutrient. However, at this time the possibility cannot be ruled out that another component in soybeans could be the active factor. No benefit is evident on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure. Thus, the direct cardiovascular health benefit of soy protein or of isoflavone supplements is minimal at best. Soy protein or isoflavones have not been shown to improve vasomotor symptoms of menopause, and results are mixed regarding slowing of postmenopausal bone loss. The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established; evidence from clinical trials is meager and cautionary as regards a possible adverse effect. For this reason, use of isoflavone supplements in food or pills is not recommended. In contrast, soy products such as tofu, "soy butter," "soy nuts," or some soy burgers should be beneficial to cardiovascular and overall health because of their high content of polyunsaturated fats, fiber, vitamins, and minerals and low content of saturated fat.⁵² Using these and other soy foods to replace foods high in animal protein that contain saturated fat and cholesterol may confer benefits to cardiovascular health.⁵³ Soy protein may also be used to increase total dietary protein intake and reduce carbohydrate or fat intake. However, much less is known about the potential impact on risk factors for CVD of high protein diets. In the meantime, these remain dynamic areas for research. The AHA will continue to monitor the results and modify its advisory statement as needed.

	Acknowledgments

 
Disclosures

None.

	References

Top Introduction Effects of Soy Protein... Soy Protein Without Isoflavones Isoflavone Effects Influence of Initial Blood... Influence of Serum Cholesterol... Effects on Lipoprotein(a) Effects on Blood Pressure Effects on Health Conditions... Conclusions References

 

1. Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M, for the American Heart Association Nutrition Committee. Circulation. 2006; 113: 1034–1044.[Abstract/Free Full Text]
2. FDA. Soy Protein and Coronary Heart Disease. In: Federal Register. 1999: 57700–57733.
3. Erdman JW Jr. AHA Science Advisory: Soy protein and cardiovascular disease: A statement for healthcare professionals from the Nutrition Committee of the AHA. Circulation. 2000; 102: 2555–2559.[Free Full Text]
4. Kritchevsky D. Vegetable protein and atherosclerosis. J Am Oil Chemists Soc. 1979; 56: 135–140.[Medline] [Order article via Infotrieve]
5. Carroll KK. Hypercholesterolemia and atherosclerosis: effects of dietary protein. Fed Proc. 1982; 41: 2792–2796.[Medline] [Order article via Infotrieve]
6. van Raaij JM, Katan MB, Hautvast JG, Hermus RJ. Effects of casein versus soy protein diets on serum cholesterol and lipoproteins in young healthy volunteers. Am J Clin Nutr. 1981; 34: 1261–1271.[Abstract/Free Full Text]
7. van Raaij JM, Katan MB, West CE, Hautvast JG. Influence of diets containing casein, soy isolate, and soy concentrate on serum cholesterol and lipoproteins in middle-aged volunteers. Am J Clin Nutr. 1982; 35: 925–934.[Abstract/Free Full Text]
8. Sirtori CR, Gatti E, Mantero O, Conti F, Agradi E, Tremoli E, Sirtori M, Fraterrigo L, Tavazzi L, Kritchevsky D. Clinical experience with the soybean protein diet in the treatment of hypercholesterolemia. Am J Clin Nutr. 1979; 32: 1645–1658.[Abstract/Free Full Text]
9. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. [see comment]. N Engl J Med. 1995; 333: 276–282.[Abstract/Free Full Text]
10. Anderson RL, Wolf WJ. Compositional changes in trypsin inhibitors, phytic acid, saponins and isoflavones related to soybean processing. J Nutr. 1995; 125: 581S–588S.[Abstract/Free Full Text]
11. Erdman JW Jr, Badger TM, Lampe JW, Setchell KD, Messina M. Not all soy products are created equal: caution needed in interpretation of research results. J Nutr. 2004; 134: 1229S–1233S.[Abstract/Free Full Text]
12. Miksicek RJ. Estrogenic flavonoids: structural requirements for biological activity. Proc Soc Exp Biol Med. 1995; 208: 44–50.[Abstract]
13. Cassidy A, Bingham S, Setchell K. Biological effects of isoflavones in young women: importance of the chemical composition of soybean products. Br J Nutr. 1995; 74: 587–601.[CrossRef][Medline] [Order article via Infotrieve]
14. Barnes S. Soy isoflavones–phytoestrogens and what else? J Nutr. 2004; 134: 1225S–1228S.[Abstract/Free Full Text]
15. Crouse JR 3rd, Morgan T, Terry JG, Ellis J, Vitolins M, Burke GL. A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med. 1999; 159: 2070–2076.[Abstract/Free Full Text]
16. Baum JA, Teng H, Erdman JW Jr, Weigel RM, Klein BP, Persky VW, Freels S, Surya P, Bakhit RM, Ramos E, Shay NF, Potter SM. Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am J Clin Nutr. 1998; 68: 545–551.[Abstract]
17. Teixeira SR, Potter SM, Weigel R, Hannum S, Erdman JW Jr, Hasler CM. Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men. [see comment]. Am J Clin Nutr. 2000; 71: 1077–1084.[Abstract/Free Full Text]
18. Vigna GB, Pansini F, Bonaccorsi G, Albertazzi P, Donega P, Zanotti L, De Aloysio D, Mollica G, Fellin R. Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial. Nutr Metab Cardiovasc Dis. 2000; 10: 315–322.[Medline] [Order article via Infotrieve]
19. Dent SB, Peterson CT, Brace LD, Swain JH, Reddy MB, Hanson KB, Robinson JG, Alekel DL. Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors. J Nutr. 2001; 131: 2280–2287.[Abstract/Free Full Text]
20. Van Horn L, Liu K, Gerber J, Garside D, Schiffer L, Gernhofer N, Greenland P. Oats and soy in lipid-lowering diets for women with hypercholesterolemia: is there synergy? J Am Diet Assoc. 2001; 101: 1319–1325.[CrossRef][Medline] [Order article via Infotrieve]
21. Teede HJ, Dalais FS, Kotsopoulos D, Liang YL, Davis S, McGrath BP. Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women. J Clin Endocrinol Metabol. 2001; 86: 3053–3060.[Abstract/Free Full Text]
22. Puska P, Korpelainen V, Hoie LH, Skovlund E, Lahti T, Smerud KT. Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial. Eur J Clin Nutr. 2002; 56: 352–357.[CrossRef][Medline] [Order article via Infotrieve]
23. Blum A, Lang N, Vigder F, Israeli P, Gumanovsky M, Lupovitz S, Elgazi A, Peleg A, Ben-Ami M. Effects of soy protein on endothelium-dependent vasodilatation and lipid profile in postmenopausal women with mild hypercholesterolemia. Clin Invest Med. 2003; 26: 20–26.[Medline] [Order article via Infotrieve]
24. Dalais FS, Ebeling PR, Kotsopoulos D, McGrath BP, Teede HJ. The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol. 2003; 58: 704–709.[CrossRef][Medline] [Order article via Infotrieve]
25. Meinertz H, Nilausen K, Hilden J. Alcohol-extracted, but not intact, dietary soy protein lowers lipoprotein (a) markedly. Arterioscler Thromb Vasc Biol. 2002; 22: 312–316.[Abstract/Free Full Text]
26. Hermansen K, Sondergaard M, Hoie L, Carstensen M, Brock B. Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. Diabetes Care. 2001; 24: 228–233.[Abstract/Free Full Text]
27. Sirtori CR, Bosisio R, Pazzucconi F, Bondioli A, Gatti E, Lovati MR, Murphy P. Soy milk with a high glycitein content does not reduce low-density lipoprotein cholesterolemia in type II hypercholesterolemic patients. Ann Nutr Metab. 2002; 46: 88–92.[CrossRef][Medline] [Order article via Infotrieve]
28. Cuevas AM, Irribarra VL, Castillo OA, Yanez MD, Germain AM. Isolated soy protein improves endothelial function in postmenopausal hypercholesterolemic women. Eur J Clin Nutr. 2003; 57: 889–894.[CrossRef][Medline] [Order article via Infotrieve]
29. Steinberg FM, Guthrie NL, Villablanca AC, Kumar K, Murray MJ. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women. Am J Clin Nutr. 2003; 78: 123–130.[Abstract/Free Full Text]
30. Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW, van der Schouw YT. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. J Am Med Assoc. 2004; 292: 65–74.[Abstract/Free Full Text]
31. West SG, Hilpery KF, Juturu V, Bordi PL, Lampe JW, Mousa SA, Kris- Etherton PM. Effects of including soy protein in a blood cholesterol lowering diet on markers of cardiac risk in men, and postmenopausal women with or without hormone replacement therapy. J Womens Health. 2005; 14: 253–262.
32. Tonstad S, Smerud K, Hoie L. A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects. Am J Clin Nutr. 2002; 76: 78–84.[Abstract/Free Full Text]
33. Jenkins DJ, Kendall CW, Vidgen E, Vuksan V, Jackson CJ, Augustin LS, Lee B, Garsetti M, Agarwal S, Rao AV, Cagampang GB, Fulgoni V 3rd. Effect of soy-based breakfast cereal on blood lipids and oxidized low-density lipoprotein. Metabolism. 2000; 49: 1496–1500.[CrossRef][Medline] [Order article via Infotrieve]
34. Wong WW, Smith EO, Stuff JE, Hachey DL, Heird WC, Pownell HJ. Cholesterol-lowering effect of soy protein in normocholesterolemic and hypercholesterolemic men. Am J Clin Nutr. 1998; 68: 1385S–1389S.[Abstract]
35. Lichtenstein AH, Jalbert SM, Adlercreutz H, Goldin BR, Rasmussen H, Schaefer EJ, Ausman LM. Lipoprotein response to diets high in soy or animal protein with and without isoflavones in moderately hypercholesterolemic subjects. [see comment]. Arterioscler Thromb Vasc Biol. 2002; 22: 1852–1858.[Abstract/Free Full Text]
36. Jenkins DJ, Kendall CW, Connelly PW, Jackson CJ, Parker T, Faulkner D, Vidgen E. Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism. 2002; 51: 919–924.[CrossRef][Medline] [Order article via Infotrieve]
37. Weggemans RM, Trautwein EA. Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis. Eur J Clin Nutr. 2003; 57: 940–946.[CrossRef][Medline] [Order article via Infotrieve]
38. Gardner CD, Newell KA, Cherin R, Haskell WL. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am J Clin Nutr. 2001; 73: 728–735.[Abstract/Free Full Text]
39. Mackey R, Ekangaki A, Eden JA. The effects of soy protein in women and men with elevated plasma lipids. Biofactors. 2000; 12: 251–257.[Medline] [Order article via Infotrieve]
40. Sanders TA, Dean TS, Grainger D, Miller GJ, Wiseman H. Moderate intakes of intact soy protein rich in isoflavones compared with ethanol-extracted soy protein increase HDL but do not influence transforming growth factor beta(1) concentrations and hemostatic risk factors for coronary heart disease in healthy subjects. Am J Clin Nutr. 2002; 76: 373–377.[Abstract/Free Full Text]
41. Wangen KE, Duncan AM, Merz-Demlow BE, Xu X, Marcus R, Phipps WR, Kurzer MS. Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab. 2000; 85: 3043–3048.[Abstract/Free Full Text]
42. Merz-Demlow BE, Duncan AM, Wangen KE, Xu X, Carr TP, Phipps WR, Kurzer MS. Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women. Am J Clin Nutr. 2000; 71: 1462–1469.[Abstract/Free Full Text]
43. Gallagher JC, Satpathy R, Rafferty K, Haynatzka V. The effect of soy protein isolate on bone metabolism. Menopause. 2004; 11: 290–298.[CrossRef][Medline] [Order article via Infotrieve]
44. Squadrito F, Altavilla D, Morabito N, Crisafulli A, D’Anna R, Corrado F, Ruggeri P, Campo GM, Calapai G, Caputi AP, Squadrito G. The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women. Atherosclerosis. 2002; 163: 339–347.[CrossRef][Medline] [Order article via Infotrieve]
45. Dewell A, Hollenbeck CB, Bruce B. The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. [see comment]. J Clin Endocrinol Metabol. 2002; 87: 118–121.[Abstract/Free Full Text]
46. Simons LA, von Konigsmark M, Simons J, Celermajer DS. Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. Am J Cardiol. 2000; 85: 1297–1301.[CrossRef][Medline] [Order article via Infotrieve]
47. Hodgson JM, Puddey IB, Beilin LJ, Mori TA, Croft KD. Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentrations: a randomized controlled trial in humans. J Nutr. 1998; 128: 728–732.[Abstract/Free Full Text]
48. Nestel PJ, Yamashita T, Sasahara T, Pomeroy S, Dart A, Komesaroff P, Owen A, Abbey M. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol. 1997; 17: 3392–3398.[Abstract/Free Full Text]
49. Nikander E, Tiitinen A, Laitinen K, Tikkanen M, Ylikorkala O. Effects of isolated isoflavonoids on lipids, lipoproteins, insulin sensitivity, and ghrelin in postmenopausal women. J Clin Endocrinol Metab. 2004; 89: 3567–3572.[Abstract/Free Full Text]
50. Nilausen K, Meinertz H. Lipoprotein(a) and dietary proteins: casein lowers lipoprotein(a) concentrations as compared with soy protein. Am J Clin Nutr. 1999; 69: 419–425.[Abstract/Free Full Text]
51. Hodgson JM, Puddey IB, Beilin LJ, Mori TA, Burke V, Croft KD, Rogers PB. Effects of isoflavonoids on blood pressure in subjects with high-normal ambulatory blood pressure levels: a randomized controlled trial. Am J Hypertens. 1999; 12: 47–53.[Medline] [Order article via Infotrieve]
52. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, Erdman JW Jr, Kris-Etherton P, Goldberg IJ, Kotchen TA, Lichtenstein AH, Mitch WE, Mullis R, Robinson K, Wylie-Rosett J, St Jeor S, Suttie J, Tribble DL, Bazzarre TL. AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Stroke. 2000; 31: 2751–2766.[Free Full Text]
53. Jenkins DJ, Kendall CW, Marchie A, Faulkner DA, Wong JM, de Souza R, Emam A, Parker TL, Vidgen E, Lapsley KG, Trautwein EA, Josse RG, Leiter LA, Connelly PW. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. J Am Med Assoc. 2003; 290: 502–510.[Abstract/Free Full Text]

This article has been cited by other articles:

				T. M. Cho, N. Peng, J. T. Clark, L. Novak, S. Roysommuti, J. Prasain, and J. M. Wyss Genistein Attenuates the Hypertensive Effects of Dietary NaCl in Hypertensive Male Rats Endocrinology, November 1, 2007; 148(11): 5396 - 5402. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sacks, F. M. Search for Related Content PubMed PubMed Citation Articles by Sacks, F. M.